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Biomedical subjects

G E Sale

Publications and source records attributed to G E Sale.

At least 37 records · Page 2Linked to original sources
PubMed1994

Parafollicular bulges, but not hair bulb keratinocytes, are attacked in graft-versus-host disease of human skin.

Graft-versus-host disease (GVHD) has been shown to preferentially attack epithelial stem cell regions in the rete ridge of epidermis, the parafollicular bulge stem cells of the hair follicle, the limbus of the eye, the basal cells of filiform papilla of the tongue and the stem cell regions of gut crypts. The parafollicular bulge, but not the papillary bulb tip, has recently been shown to be the site of follicular stem cells. The hair bulb at the tip of the papilla contains progeny of the parafollicular bulge stem cells. These progeny in turn are a proliferative population which gives rise to the hair. We asked the question: Does GVHD preferentially attack the younger, less differentiated population of cells in the parafollicular bulge but spare the also cycling, later generation of cells in the papillary bulb? We had 22 evaluable cases from our prior study of 38 biopsies of GVHD patients: 19 showed preferential bulge involvement, 2 showed both involved, 1 showed neither involved and none showed bulb positive and bulge negative. The data support a strong preference for GVHD to attack the less differentiated of two cell populations both of which are cycling, thereby supporting the hypothesis that preferred targets are related to the stem cell populations in epithelial and not just all cycling or proliferating populations.

Adult↗
PubMed1993

Positive identification of enterocytes by keratin antibody staining of sloughed intestinal tissue in severe GVHD.

Nine marrow allograft recipients who developed GVHD of the gastrointestinal tract accompanied by the passage of ropey necrotic material per rectum were studied. The material, resembling necrotic intestinal mucosa, was evaluated for the presence of epithelial cells using monoclonal antibodies for keratin and macrophages. Two keratins (AE1/AE3 and 34 beta E12) were detected within cells in all cases while macrophages were found in all but one case. In three cases, some cells were positive for both antibodies suggesting the presence of phagocytosed keratin in macrophage cytoplasm. Search for organisms with Gram and methenamine silver stains showed bacteria in six cases and fungus in one. Some cases of severe GVHD will be associated with the passage of ropey tan material grossly resembling sloughed mucosal tissue, but microscopically consisting largely of fibrin clots. The presence of free intestinal epithelial cells in this material is confirmed by the present study.

Bone Marrow Transplantation↗
PubMed1993

Splenectomy does not enhance engraftment of DLA-nonidentical marrow transplants.

Previous studies in mice and monkeys suggested that either splenic irradiation of splenectomy led to enhanced allogeneic marrow engraftment. These findings suggested that a population of radiation-resistant host cells involved in mediating marrow graft rejection are sequestered in the spleen. In this current study, the effect of splenectomy in dogs receiving 9.2 Gy total body irradiation (TBI) and unrelated dog leukocyte antigen (DLA)-nonidentical donor marrow grafts was studied. We found that splenectomy did not significantly change the incidence of graft failure as compared to that observed in previously and concurrently transplanted nonsplenectomized recipients.

Animals↗
PubMed1993

Fatal eosinophilia myalgia syndrome in a marrow transplant patient attributed to total parenteral nutrition with a solution containing tryptophan.

A 16-year-old white male with acute biphenotypic leukemia developed evidence of the eosinophilia myalgia syndrome associated with total parenteral nutritional support with solutions containing tryptophan, which were given during his initial induction chemotherapy and also after autologous marrow transplantation. He developed pronounced eosinophilia and a vasculitic skin rash, myalgias of the abdomen, upper trunk, and neck, and died of respiratory distress with no evidence of an infectious etiology. Autopsy revealed diffuse vasculitis involving the heart, lungs, kidneys, testes, spleen, liver, skin, gut wall and marrow with neuritis of gut wall nerves and ganglia. Thus, the eosinophilia myalgia syndrome can be associated with parenteral tryptophan administration.

Adolescent↗
PubMed1993

Parafollicular hair bulge in human GVHD: a stem cell-rich primary target.

We sought to determine the frequency of parafollicular hair bulge involvement in human GVHD of the skin. The parafollicular bulge was recently shown by Murphy to be a target of GVHD in the minor histoincompatible mouse GVHD model. We sought a crude estimate of this frequency by studying 541 skin biopsy reports from a 5-month period at our bone marrow transplant center. We selected 170 slides for review on the basis of a prior histological diagnosis of GVHD. Of these 41 had potentially evaluable pilar units and were recut. Three cases were considered unevaluable but the remaining 38 cases all showed positive evidence of involvement of the parafollicular hair bulge. The data confirm that the parafollicular hair bulge is involved with very high frequency in acute GVHD in humans.

Bone Marrow Transplantation↗
PubMed1992

Pharmacologic, toxicologic, and marrow transplantation studies in dogs given succinyl acetone.

A novel immunosuppressant, succinyl acetone (4,6-dioxoheptanoic acid), was studied in dogs. Results with bolus intravenous injections at doses ranging from 50 to 1600 mg/kg showed dose-dependent alpha and beta half-lives, ranging from 30 to 80 min and 7 to 27 hr, respectively. Results suggested that continuous i.v. infusion was necessary to maintain constant plasma levels. Four dogs were given 9.2 Gy total-body irradiation and autologous marrow transplants along with continuous i.v. infusion of succinyl acetone at 50, 100, 200, or 400 mg/kg/day for 21 days, and all four had rapid, sustained hematopoietic engraftment. However, two of the four dogs receiving 200 and 400 mg succinyl acetone/kg/day, respectively, developed bilateral hind-limb ataxia, with histologically confirmed cerebellar lesions in the dog given the higher dose, thus establishing a potential dose-limiting neurotoxicity. Prevention of graft-versus-host disease was studied in recipients of allogeneic marrow. Dogs were given 9.2 Gy TBI, followed by hematopoietic grafts from unrelated DLA-nonidentical or DLA-haploidentical littermate dogs. Succinyl acetone was given as continuous infusion for 21 days after transplant at doses of 100-300 mg/kg/day. Starting succinyl acetone on the day of marrow infusion in four dogs failed to prevent rapid onset of acute GVHD, and dogs survived no longer than controls. Starting succinyl acetone 3 days before transplant delayed the onset of acute GVHD and prolonged survival significantly compared with that of dogs not given postgrafting immunosuppression (P = 0.008); survival was comparable to that in previously reported dogs given either methotrexate or cyclosporine as postgrafting immunosuppression (P = 0.88 and 0.99, respectively). Seven of the sixteen allogeneic recipients developed evidence of neurotoxicity during succinyl-acetone infusion. Neurological dysfunctions were manifested by hind-limb ataxia and posterior paresis. In conclusion, succinyl acetone significantly delayed the onset of GVHD and prolonged survival of DLA-nonidentical marrow graft recipients but did not induce graft-host tolerance and was associated with dose-limiting neurotoxicity.

Animals↗
PubMed1992

Acute megakaryoblastic leukemia in children: treatment with bone marrow transplantation.

Seven children underwent BMT for acute megakaryoblastic leukemia (AMKL). They were assessed for clinical, hematologic, and cytogenetic findings as well as response to treatment. The diagnosis of AMKL was established by cytochemistry, immunophenotyping and/or platelet-peroxidase reactivity. Patients had received various prior chemotherapies. One was in first remission, another in second remission and five were in relapse at the time of admission for transplant. Marrow donors included an HLA identical sibling (one), phenotypically HLA identical unrelated (two) and partially HLA identical family members (four). Five patients achieved engraftment, one rejected the graft and died on day 20 after a second unrelated transplant and one died from infection on day 5. Two patients relapsed within the first month after transplant and died of recurrent leukemia. Another died of a second malignancy on day 2232. Two patients survive disease-free more than 3.8 and 4.3 years after transplant.

Bone Marrow Transplantation↗
PubMed1992

Abnormal CD4:CD8 ratios and delayed germinal center reconstitution in lymph nodes of human graft recipients with graft-versus-host disease (GVHD): an immunohistological study.

We searched for evidence that immunodeficiency in graft-versus-host disease (GVHD) is in part due to alloimmune damage to lymph nodes. We used immunoperoxidase techniques to stain T-cell subsets, pan-B cells, and follicular dendritic reticular cells (FDRC) in frozen sections of lymph nodes from 80 marrow graft recipients (56 with GVHD, 11 autografts, and 13 allografts without GVHD). We found that 46% of the GVHD patients had reversed CD4:CD8 ratios and only 13% of non-GVHD patients had such disturbed ratios (p = 0.006). Pan-B (CD22) cell labeling was present in the follicular regions of 73% of patients without GVHD and only 53% of patients with GVHD (p = 0.05). Focal FDRC staining was geographically concordant with clusters of B cells in 88% of cases (p less than 10(-7)). These data confirm that disturbed intranodal CD4:CD8 ratios are present more frequently in GVHD patients than in non-GVHD patients or in autografted patients. They suggest more delayed follicular B-cell reconstitution in GVHD patients. They show an extremely tight association of FDRC with clusters of B cells in the recovering lymph node, as in the developing fetal node. We hypothesize that the lack of follicular dendritic cells may contribute to dysfunctional B-cell maturation by ablating orderly antigen presentation and clonal expansion in the lymph node cortex.

B-Lymphocytes↗
PubMed1992

Proliferation rates in epidermis of patients with graft-versus-host disease, non-specific inflammation and normal skin.

There is evidence that epidermal stem cells or their early progeny may be the targets in graft-versus-host disease (GVHD). The early progeny should be a proliferating group of daughter cells more concentrated in areas just above or adjacent to stem cell regions. We have, therefore, compared proliferative rates of keratinocytes within relevant subregions of the epidermis using the AgNOR stain on biopsies from patients with GVHD, non-specific inflammatory infiltrates (NSI) and normal skin. We concurrently evaluated T cell infiltration using immunohistology on paraffin-embedded tissue with UCHL-1 antibody. Fifty-one bone marrow transplant patients were evaluated in each of three temporal groups (days 7-20 post-transplant, days 20-40 post-transplant, and days 80-100 post-transplant). In each of these groups, 5-9 patients with a histological diagnosis of GVHD were compared to similar numbers of patients with a histological diagnosis of non-specific dermatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗
PubMed1992

Evidence of cytotoxic T-cell destruction of epidermal cells in human graft-vs-host disease. Immunohistology with monoclonal antibody TIA-1.

A newly described mouse monoclonal IgG1 antibody, TIA-1, binds serine esterase-positive granule membranes of cytotoxic human T cells and is a candidate for an effector molecule involved in T-cell cytolytic mechanisms analogous to those of the perforin system. We performed immunohistologic studies on frozen human skin (n = 5) and lip (n = 21) sections as well as on control frozen sections of tonsils, purified cytolytic T (CD8) cells, and B cells using an indirect immunoperoxidase system. We found a strong association of TIA-1+ cells with CD8+ cells invading the epidermis in lip and skin lesions of graft-vs-host disease in human marrow allograft recipients, as well as a sharp geographic association of TIA+ lymphocytes with CD8+ regions in human tonsil sections. Double staining of CD8 and TIA-1 antigens with fluorescein isothiocyanate and Texas red confirmed that 80% to 90% of the CD8 cells were TIA-1+ in the epidermal infiltrates. Leu-7 activity (natural killer cell) was minimal and found in only three of 17 lip biopsy specimens. These data provide new evidence that direct cytolytic attack by donor T lymphocytes is the mechanism of epithelial target cell killing in human graft-vs-host disease.

Adolescent↗
PubMed1991

Prevention of transfusion-induced sensitization to minor histocompatibility antigens on DLA-identical canine marrow grafts by gamma irradiation of marrow donor blood.

Dogs given total-body irradiation and marrow transplants from DLA-identical littermates exhibit prompt and sustained hematopoietic engraftment. However, animals given three preceding blood transfusions from the marrow donor before transplant become sensitized and reject the marrow graft. Rejection is due to exposure to polymorphic minor non-DLA histocompatibility antigens expressed on blood mononuclear cells. We sought to determine whether heat treatment would prevent blood from sensitizing recipients in this model since heating blood to 45 degrees C for 45 min abrogates the ability of blood mononuclear cells to stimulate in mixed lymphocyte culture. Three of 4 evaluable dogs given heat-treated blood before transplant rejected their marrow grafts. To prevent possible reexpression/reacquisition of mononuclear cell functional activity in vivo after transfusion, subsequent dogs were given heated blood that was additionally exposed to 2000 cGy gamma irradiation. Eight of 10 evaluable dogs given blood treated in this fashion engrafted. Unexpectedly, 9 out of 10 evaluable dogs transfused with blood treated only with gamma irradiation also engrafted. These results demonstrate that treatment of blood with gamma irradiation alone or in combination with heat prevents transfusion-induced sensitization to minor histocompatibility antigens. Results from this canine model suggest that blood products be gamma irradiated before transfusion in patients who are transplant candidates in order to prevent sensitization to minor histocompatibility antigens and reduce the risk of marrow graft rejection.

Animals↗